Beta-lactam Agents Research Articles

How to Manage Antibiotic Allergy in Cystic Fibrosis? Epidemiologic, Diagnostic, and Therapeutic Aspects

Cystic fibrosis (CF) is a complex genetic disease with high mortality, of which 85% is a result of lung disease characterized by serious endobronchial infections. Antibiotic therapy is one of the main treatments of CF, both during acute exacerbations and as chronic maintenance medications, contributing to a prolonged survival. Since neonatal CF screening programs have been implemented universally and the longevity of patients with CF steadily increases, antibiotic hypersensitivity reactions (HSRs) are becoming more important. HSR to antibiotics in CF has been reported since the 1980s and was estimated to occur up to three times more frequently in these patients, probably owing to high rates of antibiotic exposure and boosting stimuli such as infections and inflammation. However, recent studies including large groups of CF patients with a suspicion of antibiotic allergy have used diagnostic algorithms including skin tests and drug provocation tests and showed that true incidence was much lower. The mechanism of the reactions and the clinical presentations are not different in CF than in the general population. Both the immediate and nonimmediate type HSRs are seen, and among the latter, drug fever and drug-induced hemolytic anemia are distinctive presentations. Beta-lactam (BL) agents are the most common cause, with higher rates for ureidopenicillins (piperacillin, mezlocillin, and piperacillin/tazobactam) and cephalosporins (especially ceftazidime), intermediate rates for carbapenems, and lowest rates for aztreonam, and also HSRs to aminoglycosides, macrolides, and quinolones are encountered. Since the available choices for antibiotic therapy are limited due to relevant organisms, management becomes a challenge. It is essential to evaluate the patients according to the mechanism of the HSR and determine the risk of repeat administration of the culprit drug and also safety of alternative drugs with prior skin and provocation tests. The chemical structure and side chains must be taken into account when selecting a safe alternative drug. Contrary to what was previously thought, recent data on cross-reactions between BL antibiotics showed that some BLs can be an option of treatment for patients allergic to other BLs. Desensitization is a useful procedure in immediate and some delayed reactions, if a suitable alternative antibiotic is not available.

A five-year retrospective study of the antimicrobial susceptibility pattern of Pseudomonas aeruginosa ICU clinical isolates in Al-Ahsa, Saudi Arabia.

Pseudomonas aeruginosa an opportunistic pathogen of clinical importance has been associated with infections in intensive care units worldwide. This study seeks to evaluate its susceptibility pattern over a five-year period in line with the recommended regional monitoring. Isolates were those of obtained from patients in intensive care units. Bacteria isolation was by basic bacteriological and biochemical methods. The VITEK 2 compact automated system (BioMerieux, Marcy L’Etoile, France) was used for ID confirmation and antimicrobial susceptibility assay. Data was analysed and represented as percentages as well as mean percentage ± standard error of mean (SEM). A total of 580 samples were used for the investigation. Fifty two percent (52%) of them were from males while 48% were from females. Age distribution data shows that P. aeruginosa infection was seen to be more associated in patients within the age range of 51 y and above with a total incidence was 81.25%. Colistin maintained 100% sensitivity to this bacterium throughout the duration of the study. However, for the beta lactam agents, fluoroquinolones, aminoglycosides and tigecycline, there was a decline in sensitivity from 70.4% in 2013 to 33.1% in 2017. Consequently, there was an observed growing resistance to anti-Pseudomonal drugs, from 14.7% in 2013 to 50.8% in 2017, representing a 3.5 fold increase that is alarming. Also, the mean MAR index of the antibiotic susceptibility was 0.43. The obtained results point to possibility of the isolates originating from a high risk source of contamination region where there high antibiotics use.

Determination of MIC of amoxicillin among clinical strains of Aggregatibacter actinomycetemcomitans from various geographic regions endorse the continuous use of this drug for treatment of periodontitis

ABSTRACTAim: The combination of amoxicillin and metronidazole is used in the treatment of Aggregatibacter actinomycetemcomitans (Aa)-associated periodontitis in some patients. Aa is innately susceptible to betalactam agents, but resistance or decreased susceptibility has been reported. Elucidation of the prevalence and mechanisms of resistance to betalactams in Aa is important in order to treat periodontitis patients with the most optimal antibiotic regimen.Method: 259 Aa strains were collected from patients with geographically diverse origin and serotyped with a multiplex PCR. Minimal inhibitory concentration (MIC) values were determined using the agar dilution method, with amoxicillin (range 0.00 mg/L to 8.00 mg/L) incorporated into 5 % blood agar plates with 20 mg/mL NAD. The plates were inoculated with 1 μL bacterial suspensions (104 CFU/ml), incubated in 5 % CO2 at 37 C°, and visually inspected after 24 and 48 hours. A MIC ≥ 4.00 mg/L was categorised as resistant, using EUCAST interpretative criteria for Haemophilus species.Results: None of 259 clinical Aa strains exhibited resistance towards amoxicillin. MIC-values varied from 0.25 mg/L to 2.00 mg/L. There was no clear correlation between MIC-value and serotype.Conclusion: The study showed no contraindications to the continuous use of amoxicillin as a part of the treatment strategy in patients with Aa-associated periodontitis.

In vitro synergistic effects of various combinations of vancomycin and non-beta-lactams against Staphylococcus aureus with reduced susceptibility to vancomycin

The aim of our study was to determine the potential for synergistic effect of vancomycin combined with a non–beta-lactam agent and of combinations of orally available non-beta-lactam agents against vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA). Three VISA isolates, three hVISA isolates, and two vancomycin-susceptible S. aureus (VSSA) isolates were used. The combinations included vancomycin and one of clindamycin, ciprofloxacin, gentamicin, rifampicin, or trimethoprim/sulfamethoxazole. Pairwise combinations among five non–beta-lactam agents were also tested for synergy. Synergy was determined using time-kill curves at 24h. Vancomycin combined with either ciprofloxacin or gentamicin showed synergy against some isolates of VISA, hVISA and VSSA. Vancomycin combined with trimethoprim/sulfamethoxazole showed synergy against VISA and hVISA. Among orally available non-beta-lactam agents, only ciprofloxacin combined with either clindamycin or trimethoprim/sulfamethoxazole showed synergy against one isolate of VISA.

Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens: Table 1.

Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrug-resistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs.

Clindamycin resistance among Staphylococcus aureus strains in Israel: implications for empirical treatment of skin and soft tissue infections.

The objectives of this study were to characterize isolates of Staphylococcus aureus obtained from skin and soft tissue infections in the community in Israel and to document the sensitivity patterns for commonly used antimicrobial agents. The susceptibilities of S. aureus isolates from skin and soft tissue infections in the community in Israel were reviewed to determine the appropriate empirical therapy for these infections. A total of 7221 isolates were collected during the period 2009-2012; 39% were from children (age 0-18 years). In children, S. aureus oxacillin resistance dropped from 8.4% to 3.8% (p=0.073). While inducible clindamycin resistance increased slightly from 20% to 25%, there was a prominent increase in constitutive clindamycin resistance from 0.1% to 26.8% (p=0.012). In adults, oxacillin resistance increased from 16% to 23% (p<0.001) and constitutive clindamycin resistance increased notably from 5% to 29% (p<0.001). These findings demonstrate a dramatic increase in clindamycin resistance among S. aureus isolates and suggest against the usage of clindamycin as empirical treatment for suspected S. aureus infections in Israel. Beta-lactam anti-staphylococcal agents may be given as empirical treatment for children, but should be considered according to risk factors for adults in Israel.

Detection of Extended-Spectrum Beta-Lactamase-ProducingEscherichia coliin Market-Ready Chickens in Zambia

The frequent administering of antibiotics in the treatment of poultry diseases may contribute to emergence of antimicrobial-resistant strains. The objective of this study was to detect the presence of extended-spectrum β-lactamase- (ESBL-) producing Escherichia coli in poultry in Zambia. A total of 384 poultry samples were collected and analyzed for ESBL-producing Escherichia coli. The cultured E. coli isolates were subjected to antimicrobial susceptibility tests and the polymerase chain reaction for detection of bla CTX-M, bla SHV, and bla TEM genes. Overall 20.1%, 77/384, (95% CI; 43.2–65.5%) of total samples analyzed contained ESBL-producing Escherichia coli. The antimicrobial sensitivity test revealed that 85.7% (66/77; CI: 75.7–92) of ESBL-producing E. coli isolates conferred resistance to beta-lactam and other antimicrobial agents. These results indicate that poultry is a potential reservoir for ESBL-producing Escherichia coli. The presence of ESBL-producing Escherichia coli in poultry destined for human consumption requires strengthening of the antibiotic administering policy. This is important as antibiotic administration in food animals is gaining momentum for improved animal productivity in developing countries such as Zambia.

New antibacterial agents on the market and in the pipeline

After some years of stagnation there have been several new successful developments in the field of antibacterial agents. Most of these new developments have been in conventional antibacterial classes. New drugs among the beta-lactam agents are methicillin-resistant Staphylococcus aureus (MRSA) active cephalosporins (ceftaroline and ceftobiprole) and new combinations of beta-lactam with beta-lactamase inhibitors (ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam and meropenem/RPX7009). New developments can also be observed among oxazolidinones (tedizolid, radezolid, cadazolid and MRX-I), macrolides/ketolides (modithromycin and solithromycin), aminoglycosides (plazomicin), quinolones (nemonoxacin, delafloxacin and avarofloxacin), tetracyclines (omadacycline and eravacycline) as well as among glycopeptides and lipopeptides (oritavancin, telavancin, dalbavancin and surotomycin). New agents in a very early developmental phase are FabI inhibitors, endolysines, peptidomimetics, lipid A inhibitors, methionyl-tRNA synthetase inhibitors and teixobactin.

Multicenter study of antimicrobial susceptibility of anaerobic bacteria in Korea in 2012.

BackgroundPeriodic monitoring of regional or institutional resistance trends of clinically important anaerobic bacteria is recommended, because the resistance of anaerobic pathogens to antimicrobial drugs and inappropriate therapy are associated with poor clinical outcomes. There has been no multicenter study of clinical anaerobic isolates in Korea. We aimed to determine the antimicrobial resistance patterns of clinically important anaerobes at multiple centers in Korea.MethodsA total of 268 non-duplicated clinical isolates of anaerobic bacteria were collected from four large medical centers in Korea in 2012. Antimicrobial susceptibility was tested by the agar dilution method according to the CLSI guidelines. The following antimicrobials were tested: piperacillin, piperacillin-tazobactam, cefoxitin, cefotetan, imipenem, meropenem, clindamycin, moxifloxacin, chloramphenicol, metronidazole, and tigecycline.ResultsOrganisms of the Bacteroides fragilis group were highly susceptible to piperacillin-tazobactam, imipenem, and meropenem, as their resistance rates to these three antimicrobials were lower than 6%. For B. fragilis group isolates and anaerobic gram-positive cocci, the resistance rates to moxifloxacin were 12-25% and 11-13%, respectively. Among B. fragilis group organisms, the resistance rates to tigecycline were 16-17%. Two isolates of Finegoldia magna were non-susceptible to chloramphenicol (minimum inhibitory concentrations of 16-32 mg/L). Resistance patterns were different among the different hospitals.ConclusionsPiperacillin-tazobactam, cefoxitin, and carbapemems are highly active β-lactam agents against most of the anaerobes. The resistance rates to moxifloxacin and tigecycline are slightly higher than those in the previous study.

Development of a combination antibiogram for Pseudomonas aeruginosa bacteremia in an oncology population.

Development of a combination antibiogram to identify combinations of antibiotics that have the highest likelihood of attaining one active agent in the empiric management of presumed Pseudomonas aeruginosa bacteremia. Patients with cancer and P. aeruginosa bacteremia from January 1 to December 31, 2012 were included in this analysis. The primary outcome was identification of effective combinations of beta-lactam and non-betalactam agents. An effective combination was defined as one which achieved in-vitro activity to greater than or equal to 85% of isolates collected. Furthermore, the addition of the non-beta-lactam agent was required to increase the in-vitro activity by at least 5% over beta-lactam monotherapy. Multiple secondary outcomes were evaluated. One hundred and twenty-three P. aeruginosa isolates were included from 99 patients. Single agent beta-lactam sensitivities ranged from 72.4 to 79.7%. Combination regimen sensitivities ranged from 73.5 to 96.7%. All combination regimens that included a beta-lactam plus an aminoglycoside were found to be effective per the study definition. Independent risk factors for MDR P. aeruginosa were receipt of intravenous (IV) antibiotics within 90 days and hospital length of stay (LOS) greater than or equal to five days. Increasing the number of antibiotics received was associated with a decrease in survival to hospital discharge. Effective combination regimens included all beta-lactam aminoglycoside regimens. Receipt of IV antibiotics within 90 days and hospital LOS greater than or equal to five days were independent risk factors for MDR isolates.

Limitations of beta-lactam therapy for infections caused by susceptible Gram-positive bacteria

Penicillin and related beta-lactam agents have been the most widely used and most important antimicrobials in medical history, and remain the recommended therapy for many infectious diseases 85 years after the discovery of penicillin by Alexander Fleming. Yet the efficacy of these agents has been undermined by two factors - the emergence of clinically significant resistance to the antimicrobial activity of these agents, and clinical situations in which these drugs may be suboptimal (even though the bacterial pathogens are not "resistant" to the drugs). Observations in experimental infection models in animals (group A streptococcal myositis, pneumococcal meningitis and pneumonia, group B streptococcal sepsis) and in some cases clinical studies suggest that monotherapy with beta-lactam antibiotics may be inferior to treatment with other types of antibiotics, alone or in combination with beta-lactams - even in situations where the bacterial pathogens remain fully "susceptible" to beta-lactams invitro.

A severe cutaneous reaction caused by acetaminophen in a pediatric patient

A small girl of 2 years-6-months was admitted to our hospital for widespread rash on the face, trunk and limbs that had begun 24 hours previously; she also complained arthralgia of small and large joints and fever. She had received acetaminophen at home for 3 days because of febrile gastroenteritis. Family history was positive for allergy (mother had allergic rhinitis and beta-lactam drug allergy). The rash was widespread and included confluent purpuric macules on the trunk, limbs and on the face. There was no mucosal involvement and no skin detachment. Blood work up showed a slight increase of CRP (1.1 mg/dl) and ESR (34 mm/1h), as well as elevated tryptase (19.2 ng/ml – nv 0-5) and total IgE (178 KU/I). Liver and kidney function was normal as well as electrolytes and coagulation; screening for autoimmunity (ANA, ENA, AMA, antiDNA, ASMA, ANCA, C3, C4, rheumatoid factor) and the infectious valutation (Ab anti CMV, EBV, HHV6 and 8, Mycoplasma, postnasal swab for virus) were negative. Skin biopsy was compatible with vasculitis from possible adverse drug reaction (slight oedema in the upper dermis associated with perivascular lymphohistiocytic infiltrate, without a relevant presence of eosinophils). The patient was treated with methylprednisolone with rapid alleviation of symptoms and a complete resolution within 10 days. The pediatric literature reports numerous hypersensitivity reactions with vascular involvement, caused by NSAIDs and beta-lactam agents (1), while cases regarding the assumption of acetaminophen are rare. Although adverse cutaneous reactions to acetaminophen are rare, considering the widespread use of this drug in pediatric age, we believe that the description of this case is useful inasmuch as a prompt diagnosis and an early treatment as well as drug suspension are crucial for improving the prognosis. Authors’ details Allergy and Immunology Unit, Niguarda Hospital, Italy. Niguarda Hospital, Pediatric Ward, Italy. Niguarda Hospital, Burn Unit, Italy.

Doripenem Versus Meropenem For Empirical Antimicrobial Therapy In High Risk Febrile Neutropenic Patients With Hematological Malignancies: A Randomized, Controlled Trial

Background Febrile neutropenia (FN) is often observed in the treatment of hematological malignancies including acute leukemia (AL). The pathogens of systemic infection are frequently unknown in FN patients. Carbapenem antibiotics are good candidates with a potent and broad antimicrobial activity against gram-positive and gram-negative bacteria including Pseudomonas aeruginosa. These antimicrobial agents are recommended to use early and sufficiently as empiric therapy for high-risk FN patients accompanied with profound neutropenia anticipated to &gt; 7days. In the IDSA guideline published in 2010 on the use of antimicrobial agents in neutropenic patients, monotheapy with an anti-pseudomonal beta-lactam agent, such as cefepime (CFPM), meropenem (MEPM), imipenem-cilastatin (IPM) or piperacillin-tazobactam (TAZ/PIPC), is recommended as empiric therapy for high-risk FN patients. Several antimicrobial agents including MEPM, IPM or CFPM have been studied as empirical therapy for FN. However, limited data are available concerning the efficacy and safety of doripenem (DRPM), one of the carbapenem antibiotics, in FN with hematological malignancy. Methods We conducted a randomized, cooperative group, open-label trial comparing DRPM (1g, q8h IV) with MEPM (1g, q8h IV) as the first line empirical antimicrobial treatment for 165 hospitalized high-risk FN patients with AL (AML: n=90, APL: n=25, MDS-AML: n=13, ALL: n=35, ATL: n=2) during or after induction or consolidation chemotherapy (DRPM: n=83, MEPM: n=82). These study drugs were administered at least for 3 days without toxicity. The primary endpoint was response to treatment defined as complete defervescence by day 7 with improvement of infection-related symptoms and laboratory findings. We also evaluated the efficacy (resolution of fever by monotherapy at day 3 to 5, survival at day 30) and the safety of each drug, as a secondary endpoint. Results At the time of enrolment, there were no significant differences in the demographics or baseline characteristics, including as age, sex, body weight, underlying hematological malignancies, duration of initial antimicrobial therapy, median duration of severe neutropenia (neutrophil count &lt; 100×106/L) and MASCC score, between the two groups. The response rate at day 7 was not significantly different between the two arms (DRPM: 75.8%, MEPM: 64.5% (p=0.14)). The resolution of fever by monotherapy at day 3 to 5 (DRPM: 58.6%, MEPM: 45.2% (p=0.10)), or survival at day 30 (DRPM: 97.6%, MEPM: 98.7% (p=0.33)) was not significantly different in the two groups. Adverse events were minimal in the two groups, and most of patients could continue the treatment by study drugs for 7days. Conclusions We could prove the non-inferiority of DRPM in comparison with MEPM for the initial treatment in FN patients with hematological malignancies. Both drugs were well tolerated as the first line empiric therapy for high-risk FN patients. Disclosures: No relevant conflicts of interest to declare.

Comparative Activities of Telavancin Combined with Nafcillin, Imipenem, and Gentamicin against Staphylococcus aureus

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

Skin Testing For Beta-Lactam Antibiotics: Impact of the Availability of a Major Determinant

Beta-lactam antibiotics are very effective agents for a variety of infections. In patients with beta-lactam allergy, these drugs are withheld due to fear of subsequent allergic reactions. Therefore, increasing their exposure to broad spectrum antibiotics, which are more costly, have greater side effects, and increase the risk of developing resistant organisms. Up to 90% of patients with a proposed beta-lactam sensitivity can tolerate beta lactam agents after appropriate evaluation. Skin testing to beta-lactam agents is the gold standard in evaluating patients with type I, immediate hypersensitivity reactions. The robust negative predictive value of this test has yet to be surpassed by any other testing modality currently available.

Cefozoplan, Meropenem, or Imipenem-Cilastatin Versus Cefepime As an Empirical Therapy in High Risk Febrile Neutropenic Adult Patients: A Multicenter Prospective Randomized Trial

AbstractAbstract 1037▪▪This icon denotes a clinically relevant abstract Background:In the IDSA guideline published in 2010 on the use of antimicrobial agents in neutropenic cancer patients, monotherapy with an anti-pseudomonal beta-lactam agent, such as cefepime (CFPM), carbapenem [meropenem (MEPM) or imipenem-cilastatin (IPM)], or piperacillin-tazobactam, is recommended as an empiric therapy for high risk febrile neutropenia (FN) patients. There have been few reports on the efficacy of cefozopran (CZOP), one of the 4thgeneration beta-lactams, in the treatment of such patients. We conducted an open-label randomized controlled study to evaluate the clinical efficacy of CZOP, MEPM, or IPM in high-risk FN adult patients with hematologic malignancies and solid tumors, using CFPM as a control. Methods:In this trial, 386 patients registered from 23 centers were randomized to receive either 4thgeneration beta-lactam (CFPM 2g, q12h IV or CZOP 2g, q12h IV) or carbapenem (MEPM 1g, q12h IV or IPM 1g, q12h IV). The primary endpoint was response to treatment defined as complete defervescence by day 7 with improvement in infection-related symptoms and laboratory findings. The clinical data were analyzed both by intention to treat and per protocol. We also evaluated the efficacy of each of the initial four drugs at days 3 to 5as a secondary endpoint. Results:386 patients received the assigned antibiotic (CFPM: n=95, CZOP: n=98, MEPM: n=96, IPM: n=97) and 377 were evaluated for efficacy (CFPM: n=94, CZOP: n=95, MEPM: n=94, IPM: n=94). The 4 groups were comparable in terms of the baseline characteristics, including as age (median: 59 years (range: 17–87)), sex (male: n=215, female: n=171), body weight (median: 55 kg (range: 32–100)), underlying malignancy (leukemia: n=212 (54.9%), lymphoma: n=122 (31.6%), multiple myeloma: n=37 (9.6%), myelodysplastic syndrome: n=6 (1.6%), and other malignancy: n=9 (2.3%)), duration of initial antibiotic therapy (median: 7 days (range: 1–29)), median duration of severe neutropenia (neutrophil count < 100×106/L) (median: 6 days (range: 0–56)) and MASCC score (median: 21 (range:3–26)). Only neutrophil count at onset of IPM was significantly lower compared to the other treatments (CFPM: 38×106/L, CZOP: 35 x106/L, MEPM: 18×106/L, and IPM: 3×106/L, p=0.003). In intention-to-treat analysis, the response rates at day 7 were not significantly different among the four arms (CFPM: 63%, CZOP: 59%, MEPM: 61%, IPM: 69% (P=0.52)). The three antibiotics investigated in this trial were as effective as the reference agent, CFPM, in both the intention-to-treat and per-protocol populations. In both the intention-to-treat and per protocol analyses, success rates of the initial therapy at days 3 to 5 were not significantly different among four drugs [CFPM: 52 and 54%, CZOP: 46 and 47%, MEPM: 54 and 55%, IPM: 49 and 53% (P=0.70 and 0.68, respectively)]. Conclusions:CZOP, MEPM, and IPM were as effective as CFPM for adult FN patients with hematological malignancies and solid tumors as an empiric therapy. Disclosures:Tamura:Kyowa Hakko Kirin Co., Ltd,: Consultancy.

Detection and Characterization of VIM-31, a New Variant of VIM-2 with Tyr224His and His252Arg Mutations, in a Clinical Isolate of Enterobacter cloacae

We report the first description of the metallo-β-lactamase VIM-31, a new variant of VIM-2 with Tyr224His and His252Arg mutations, in Enterobacter cloacae 11236, which was isolated from blood specimens of a patient with colonic adenocarcinoma in Belgium. bla(VIM-31) was found on a class 1 integron located on a self-transferable but not typeable 42-kb plasmid. Compared to values published elsewhere for VIM-2, the purified VIM-31 enzyme showed weaker catalytic efficiency against all the tested beta-lactam agents (except for ertapenem), resulting from lower k(cat) (except for ertapenem) and higher K(m) values for VIM-31.

Safety and Effectiveness of Penicillin Allergy Evaluation in the Pre-Lung Transplant Patient Population

Pre-lung transplant patients reporting penicillin allergy present a unique population that would benefit from an Allergy consultation. Appropriate use of antimicrobial agents decrease the risk of developing pathogenic and opportunistic infections. Penicillin is the only beta-lactam antimicrobial agent with a standardized skin test. A detailed history, exam, skin tests and ingestion challenge can be performed safely in this vulnerable patient population.

Index of Suspicion in the Nursery

Twins are born at 37-5/7 weeks gestation to a 41-year-old G4P2 woman who had unremarkable serology results. The delivery is via cesarean section because of a nonreassuring fetal heart rate. Twin B appears to be acrocyanotic and initially requires positive-pressure ventilation for 30 seconds before being able to maintain her oxygen saturation on her own. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She also appears to be “jittery,” and her screening glucose concentration is 24 mg/dL (1.3 mmol/L). She consumes 20 mL of infant formula and a 10% dextrose (D10) infusion is begun at a rate of 60 mL/kg per day. Three hours after birth, a follow-up glucose evaluation measures 30 mg/dL (1.7 mmol/L), prompting administration of a 4-mL/kg bolus of D10 over 20 minutes and increase of the maintenance infusion rate to 100 mL/kg per day. Six hours after birth, glucose measures 80 mg/dL (4.4 mmol/L), and the infusion rate is decreased to 60 mL/kg per day. She is transferred to a hospital that has a neonatal intensive care unit (NICU) for close monitoring. On transfer, the oxygen saturation dips into the upper 80s/lower 90s, and nasal cannula administration of oxygen is initiated. Furthermore, during transfer (8 to 9 hours after birth), the blood glucose value is 44 mg/dL (2.4 mmol/l), so the D10 infusion rate is increased back to 100 mL/kg per day. On arrival at the second hospital, her oxygen saturation is about 85% and glucose is 50 mg/dL (2.8 mmol/L). In the NICU, she receives noninvasive respiratory support as well as 15% dextrose (D15) at a rate of 70 mL/kg per day. Twin A remains stable and continues to receive routine newborn care in the newborn nursery of the first hospital. Two days after birth, twin B continues to have glucose …

Clinical manifestations and outcome of skin infections caused by the community‐acquired methicillin‐resistant Staphylococcus aureus clone ST80‐IV

Several Panton-Valentin leukocidin-positive clones of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are spreading worldwide. The European clone ST80-IV is the main CA-MRSA clone in Europe. There is no reported study of the specific clinical manifestations and outcome of skin infections caused by the clone ST80-IV, using strict definitions of skin diseases. Single-centre observational prospective cohort of S. aureus skin infections caused by the clone ST80-IV. From November 1999 to October 2009, we diagnosed skin infections due to the clone ST80-IV in 20 patients (median age 28 years, median 27; range 1-66). All the isolates had all the following characteristics: lukPV, etd and edin gene-positive, agr 3 allele, spa-type t044 and ST80. All the isolates were resistant to beta-lactam agents, kanamycin, tetracycline and fusidic acid. During the study period, the 20 patients had the following manifestations: 19 primary abscesses (18 single abscess and one patient with two), eight furuncles, four folliculitis, one case of cellulitis, one wound infection and one felon. Surgical treatment and drainage was required for all the primary abscesses. The infections occurred mainly in the perineal area (50%). No secondary infections occurred in family members. Despite strict hygiene measures, systemic antibiotics and nasal mupirocine, four patients (20%) had recurrent skin infections over a period of a few months to 6 years. The CA-MRSA clone ST80-IV is responsible for suppurative skin infections such as furuncles and abscesses, which can recur over a period of several years.